Computer Study of the Ionic Mechanisms of Organophosphorous-Caused Long- QT Syndrome (LQTS)

摘要

An important clinical marker of organophosphorous (OP)-caused cardiac toxicity is long-QT syndrome, the prolongation of the repolarization period in the ventricles, as measured in an electrocardiogrant The primary membrane currents responsible for this condition are two potassium currents, IKr and IKs This computer simulation investigated the effect of the modulation of the membrane currents most likely affected by the OP on the action potential in a two-dimensional slab of cardiac tissue. We have shown that modulation and reduction of the potassium currents, changes in the background current, and calcium overload of the cells mimic the experimentally observed change in slope of the depolarization in the presence of OPs as well as the prolongation and change in the shape of the plot of repolarization voltage vs. time. These changes are precursors to the onset of Torsade de Pointes and ventricular fibrillation and suggest the required pharmacology of antidotes for force protection. Based on these results, an estimated dose-response curve is presented.